Two distinct autosomal recessive forms of galactosemia occur in man. Galactokinase deficiency results in cataract formation. Galactose-1-phosphate uridyltransferase (transferase) deficiency produces liver and neurologic disease as well as cataracts and can be fatal. This project will investigate the metabolic consequences and the molecular basis of malfunctioning transferase proteins that now have been identified in 16 different galactosemic families. Cell culture lines derived from patients with transferase deficiency will be used to search for metabolic abnormalities secondary to the primary enzyme defect. Non-functional enzyme proteins of transferase deficient individuals will be studied to characterize the molecular basis of catalytic malfunction.